Method and system for modifying eye tissue and intraocular lenses

ABSTRACT

A system for ophthalmic surgery includes a laser source configured to deliver an ultraviolet laser beam comprising laser pulses having a wavelength between 320 nm and 370 nm to photodecompose one or more intraocular targets within the eye with chromophore absorbance. The pulse energy, the pulse duration, and the focal spot are such that an irradiance at the focal spot is sufficient to photodecompose the one or more intraocular targets without exceeding a threshold of formation of a plasma and an associated cavitation event. An optical system operatively coupled to the laser source and configured to focus the ultraviolet laser beam to a focal spot and direct the focal spot in a pattern into the one or more intraocular targets. The optical system focuses the laser beam at a numerical aperture that provides for the focal spot to be scanned over a scan range of 6 mm to 10 mm.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of U.S. patent applicationSer. No. 12/987,069, filed Jan. 7, 2011, which claims the benefit under35 U.S.C. § 119 of U.S. provisional Patent Application Ser. No.61/293,357, filed Jan. 8, 2010. The foregoing applications are herebyincorporated by reference into the present application in their entiretyas if fully set forth herein.

BACKGROUND OF THE INVENTION

Cataract extraction is one of the most commonly performed surgicalprocedures in the world. A cataract is the opacification of thecrystalline lens or its envelope—the lens capsule—of the eye. It variesin degree from slight to complete opacity that obstructs the passage oflight. Early in the development of age-related cataract the power of thelens may be increased, causing near-sightedness (myopia), and thegradual yellowing and opacification of the lens may reduce theperception of blue colors as those wavelengths are absorbed andscattered within the crystalline lens. Cataract typically progressesslowly to cause vision loss and are potentially blinding if untreated.

Treatment is performed by removing the opaque crystalline lens andreplacing it with an artificial intraocular lens (IOL). An estimated 3million cases are presently performed annually in the United States and15 million worldwide. This market is composed of various segmentsincluding intraocular lenses for implantation, viscoelastic polymers tofacilitate surgical maneuvers, disposable instrumentation includingultrasonic phacoemulsification tips, tubing, and various knives andforceps.

Modern cataract surgery is typically performed using a technique termedphacoemulsification in which an ultrasonic tip with associatedirrigation and aspiration ports is used to sculpt the relatively hardnucleus of the lens to facilitate it removal through an opening made inthe anterior lens capsule termed anterior capsulotomy or more recentlycontinuous curvilinear capsulorhexis (CCC). Finally, a syntheticfoldable intraocular lens is inserted into the remaining lens capsule ofthe eye through a small incision.

One of the most technically challenging and critical steps in theprocedure is making the capsulorhexis. This step evolved from an earliertechnique termed can-opener capsulotomy in which a sharp needle was usedto perforate the anterior lens capsule in a circular fashion followed bythe removal of a circular fragment of lens capsule typically in therange of 5-8 mm in diameter. This facilitated the next step of nuclearsculpting by phacoemulsification. Due to a variety of complicationsassociated with the initial can-opener technique, attempts were made byleading experts in the field to develop a better technique for removalof the anterior lens capsule preceding the emulsification step.

The concept of the continuous curvilinear capsulorhexis is to provide asmooth continuous circular opening through which not only thephacoemulsification of the nucleus can be performed safely and easily,but also for easy insertion of the intraocular lens. It provides both aclear central access for insertion, a permanent aperture fortransmission of the image to the retina by the patient, and also asupport of the IOL inside the remaining capsule that would limit thepotential for dislocation.

Problems may develop related to inability of the surgeon to adequatelyvisualize the capsule due to lack of red reflex, to grasp it withsufficient security, to tear a smooth circular opening of theappropriate size and in the correct location without creating radialrips and extensions. Also present are technical difficulties related tomaintenance of the anterior chamber depth after initial opening, smallsize of the pupil, or the absence of a red reflex due to the lensopacity. Some of the problems with visualization have been minimizedthrough the use of dyes such as methylene blue or indocyanine green.Additional complications arise in patients with weak zonules (typicallyolder patients) and very young children that have very soft and elasticcapsules, which are very difficult to controllably and reliably ruptureand tear.

Many cataract patients have astigmatic visual errors. Astigmatism canoccur when the corneal curvature is unequal in all directions. Nowadays,IOLs are used to correct for astigmatism but require precise rotationaland central placement. Additionally, IOLs are not used for correctionbeyond 5D of astigmatism, even though many patients have more severeaberrations. Higher correction beyond 5D is required to reshape thecornea to become more spherical. There have been numerous approaches,including Corneaplasty, Astigmatic Keratotomy, Corneal Relaxing incision(CRI) and Limbal Relaxing Incision (LRI). Except the Corneaplasty, allprocedures are done by placing corneal incisions in a well definedmanner and depth to allow the cornea to change shape to become morespherical. Nowadays, these delicate cuts are placed manually with itsimplication on its limited precision.

But, not only cuts are desired for ophthalmic therapies. There is alsothe need for more gentle modifications of the eye tissue which result inweakening of the tissues mechanical properties and or changes of theoptical properties of the treated tissue. In this case, the effectshould be gentle enough to allow structural modifications of the eyetissue without mechanical disruption. Ding et al. (IOVS, 2008 (49), 12,pp 5532-5539) showed modification of corneal tissue with sub-rupturefemtosecond laser pulses and could demonstrate changes in the refractiveindex by about 1% by applying diffraction patterns into the cornealtissue. The practical application of Ding's technique is althoughlimited by the need to apply 100,000,000 laser pulses per cubicmicrometer of treated tissue.

Vogel et al. (US 2010/0163540 A1) describes a method for machining andcutting of transparent material with temporal smooth laser beams togenerate a low density plasma without the formation of plasmaluminescence. In the teaching, they describe that linear absorption ofthe exposed material is especially to be avoided as it leads to therandom generation of seeding electrons which in turn generates astochastic variation in the plasma threshold. Additionally, theydescribe that the low density plasma formation is always associated withthe formation of cavitation bubbles.

This is in strong contrast to the present invention in which two workingregimens are described. It was discovered that using a laser wavelengththat has some linear absorption in the target tissue enables to createextremely low threshold effect. Additionally, a temporal smooth pulseshape is not required in the current invention. Also, the formation of acavitation bubble is not desired in one embodiment of the invention asthe effect is induced by linear absorption enhanced photodecomposition.Also, Vogel's data show that there is still more than one orderdifference in achieving plasma formation when comparing IR femtosecondlasers and 355 sub-ns laser. In our embodiment, due to the use of thelinear absorption of tissue intrinsic chromophores (or via the additionof exogenous chromophores) the energy threshold for the 355 nmsub-nanosecond laser is even slightly lower when compared to femtosecondlaser pulses using the same numerical aperture optics.

Braun et al. (DE 198 55 623 C1) describes a method for precise machininginside of glass using a laser with wavelength outside the transmissionplateau of the glass. This laser is then used to specifically creatematerial defects inside the glass without comprising the surface. Thismethod allows them to place material defects closer to the surfacewithout damaging the surface itself. No surface effects are described.It also does not create any cavitation event as its used only on glassin which no cavitation bubble is formed.

Koenig et al. (WO 2007/057174) claims a system for the surgicalintervention of the eye by using femtosecond laser pulses in the UVspectral range. In his teaching, he describes the use of highernumerical apertures of 0.8 for his invention which lowers the thresholdsignificantly into the nanoJoule regimen. But, he makes the transfer ofthis system into a useable product so difficult as it is opticallydifficult to have these numerical apertures combined with a wide scanranges of 6 to 10 mm typically used for ophthalmic applications. Also,the generation of femtosecond UV laser pulses is technicallychallenging.

Therefore, methods, techniques, and an apparatus to advance the standardof care of the ophthalmic patient are needed.

SUMMARY OF THE INVENTION

Accordingly, this disclosure provides systems and methods for use insuitable ophthalmic laser surgery systems so as to obviate one or moreproblems due to limitations and disadvantages of the related art. Oneembodiment is directed to a system for ophthalmic surgery, comprising alaser source configured to deliver a laser beam comprising a pluralityof laser pulses having a wavelength between about 320 nanometers andabout 430 nanometers and a pulse duration between about 1 picosecond andabout 100 nanoseconds; and an optical system operatively coupled to thelaser source and configured to focus and direct the laser beam in apattern into one or more intraocular targets within an eye of a patient,such that interaction between the one or more targets and the laserpulses is characterized by linear absorption enhanced photodecompositionwithout formation of a plasma or associated cavitation event. Thewavelength may be about 355 nm. The pulse duration may be between about400 picoseconds and about 700 picoseconds. The pulses may have a pulseenergy between about 0.01 microJoules and about 500 microJoules. Thepulses may have a pulse energy of between about 0.5 microJoules andabout 10 microJoules. The plurality of laser pulses may have arepetition rate of between about 500 Hertz and about 500 kiloHertz. Theoptical system may be configured to focus the laser beam to create abeam diameter of between about 0.5 microns and about 10 microns withinthe one or more intraocular targets. At least one of the one or moreintraocular targets may be selected from the group consisting of acornea, a limbus, a sclera, a lens capsule, a crystalline lens, and asynthetic intraocular lens implant. The pattern may be configured tocreate one or more physical modifications, such as cuts (incisions) andrefractive index changes, in the intraocular target in a configurationselected from the group consisting of corneal relaxing incisions, limbalrelaxing incisions, astigmatic keratotomies, and capsulotomies. Theoptical system and laser source may be configured to structurally alterat least one of the one or more intraocular targets such that an indexof refraction of the altered tissue structure target is changed.

Another embodiment is directed to a system for ophthalmic surgery,comprising a laser source configured to deliver a laser beam comprisinga plurality of laser pulses having a wavelength between about 320nanometers and about 430 nanometers and a pulse duration between about 1picosecond and about 100 nanoseconds; and an optical system operativelycoupled to the laser source and configured to focus and direct the laserbeam in a pattern into one or more tissue structure targets within aneye of a patient, such that interaction between the one or more targetsand the laser pulses is characterized by localized formation of a plasmathat is facilitated by linear absorption. The wavelength may be about355 nm. The pulse duration may be between about 400 picoseconds andabout 700 picoseconds. The pulses may have a pulse energy between about0.01 microJoules and about 500 microJoules. The pulses may have a pulseenergy of between about 0.5 microJoules and about 10 microJoules. Theplurality of laser pulses may have a repetition rate of between about500 Hertz and about 500 kiloHertz. The optical system may be configuredto focus the laser beam to create a beam diameter of between about 0.5microns and about 10 microns within the one or more tissue structuretargets. At least one of the one or more tissue structure targets may beselected from the group consisting of a cornea, a limbus, a sclera, alens capsule, a crystalline lens, and a synthetic intraocular lensimplant. The pattern may be configured to create one or more cuts in theintraocular target that is tissue structure target in a configurationselected from the group consisting of corneal relaxing incisions, limbalrelaxing incisions, astigmatic keratotomies, and capsulotomies.

Another embodiment is directed to a system for ophthalmic surgery,comprising a laser source configured to deliver a laser beam comprisinga plurality of laser pulses having a wavelength between about 320nanometers and about 430 nanometers and a pulse duration between about 1picosecond and about 100 nanoseconds; and an optical system operativelycoupled to the laser source and configured to focus and direct the laserbeam in a pattern into one or more targets within an eye of a patient,such that interaction between the one or more targets and the laserpulses is characterized by linear absorption enhanced photodecompositionwithout formation of a plasma or associated cavitation event. Thepattern may be configured such that the operation of the optical systemand laser source causes physical alteration of the one or more targets.The physical alteration may be manifested as a change in refractiveindex of the one or more targets or one or more incisions. At least oneof the one or more targets may be a cornea or an artificial intraocularlens. The physical alteration may be configured to change the refractiveprofile of the target.

Another embodiment is directed to a system for ophthalmic surgery,comprising a laser source configured to deliver a laser beam comprisinga plurality of laser pulses having a wavelength between about 320nanometers and about 430 nanometers and a pulse duration between about 1picosecond and about 100 nanoseconds; an optical system operativelycoupled to the laser source and configured to focus and direct the laserbeam in a pattern into one or more tissue structure targets within aneye of a patient, such that interaction between the one or more targetsand the laser pulses is characterized by linear absorption enhancedphotodecomposition without formation of a plasma or associatedcavitation event; and an integrated imaging subsystem that captures in aconfocal arrangement back-reflected light from a sample provided by thelaser source. The laser pulses may induce fluorescence that is collectedby the imaging subsystem. The system may be configured to provideinterleaved lower energy pulses for imaging and higher energy pulses fortreatment. The imaging subsystem may comprise an optical coherencetomography system, a Purkinje imaging system, and/or a Scheimpflugimaging system. The system may further comprise a controller configuredto determine the locations & shapes of ocular structures, to determinepattern placement and/or laser parameters, and position the patternswithin the defined targets.

Another embodiment is directed to a system for ophthalmic surgery,comprising a laser source configured to deliver a laser beam comprisinga plurality of laser pulses having a wavelength between about 320nanometers and about 430 nanometers and a pulse duration between about 1picosecond and about 100 nanoseconds; an optical system operativelycoupled to the laser source and configured to focus and direct the laserbeam in a pattern into one or more tissue structure targets within aneye of a patient, such that interaction between the one or more targetsand the laser pulses is characterized by linear absorption enhancedphotodecomposition without formation of a plasma or associatedcavitation event; and an exogenous chromophore introduced to the targetstructure to create/enhance linear absorption. The exogenous chromophoremay be trypan blue.

Another embodiment is directed to a system for ophthalmic surgery,comprising a laser source configured to deliver a laser beam comprisinga plurality of laser pulses having a wavelength between about 320nanometers and about 430 nanometers and a pulse duration between about 1picosecond and about 100 nanoseconds; and an optical system operativelycoupled to the laser source and configured to focus and direct the laserbeam in a pattern into one or more intraocular targets within an eye ofa patient, such that interaction between the one or more targets and thelaser pulses is characterized by linear absorption enhancedphotodecomposition without formation of a plasma or associatedcavitation event; with the addition of a second laser source configuredto fragment the lens utilizing a wavelength between about 800 nm andabout 1100 nm. The second laser may be a pulsed infrared laser. Thesecond laser may have a pulse duration between about 1 picosecond andabout 100 nanoseconds. The second laser may be a Q-switched Nd:YAGlaser.

Another embodiment is directed to a system for ophthalmic surgery of aneye of a patient, which comprises: a laser source configured to deliveran ultraviolet laser beam comprising a plurality of ultraviolet laserpulses having a wavelength between 320 nanometers and 370 nanometers tophotodecompose one more intraocular targets within the eye withchromophore absorbance, a pulse duration between 1 picosecond and 100nanoseconds, and a pulse energy between 0.01 microJoules and 500microJoules; and an optical system operatively coupled to the lasersource and configured to focus the ultraviolet laser beam to a focalspot and direct the focal spot in a pattern into the one or moreintraocular targets selected from the group consisting of a cornea, alimbus, a sclera, a lens capsule, a crystalline lens, and a syntheticintraocular lens implant; the pulse energy, the pulse duration, and thefocal spot being configured such that an irradiance of the ultravioletlaser beam at the focal spot is sufficient to photodecompose the one ormore intraocular targets with chromophore absorbance without exceeding athreshold of formation of a plasma and an associated cavitation event,wherein the ultraviolet laser beam is focused by the optical system atthe one or more intraocular targets at a numerical aperture thatprovides for the focal spot of the laser beam to be scanned over a scanrange of 6 mm to 10 mm in a direction lateral to a Z-axis that isaligned with the laser beam. The numerical aperture of the system isless than 0.6, preferably between 0.05 to 0.4.

Another embodiment is directed to a system for ophthalmic surgery of aneye of a patient, which comprises: a laser source configured to deliveran ultraviolet laser beam comprising a plurality of ultraviolet laserpulses having a wavelength, a pulse duration, and a pulse energy,wherein the plurality of ultraviolet laser pulses has a wavelengthbetween 320 and 370 nanometers to photodecompose one or more intraoculartargets within the eye with chromophore absorbance; and an opticalsystem operatively coupled to the laser source and configured to focusthe ultraviolet laser beam to a focal spot and direct the focal spot ina pattern into the one or more intraocular targets selected from thegroup consisting of a cornea, a limbus, a sclera, a lens capsule, acrystalline lens, and a synthetic intraocular lens implant; the pulseenergy, the pulse duration, and the focal spot being configured suchthat an irradiance of the ultraviolet laser beam at the focal spot issufficient to photodecompose the one or more intraocular targets withchromophore absorbance without exceeding a threshold of formation of aplasma and an associated cavitation event, and wherein the ultravioletlaser beam is focused by the optical system at the one or moreintraocular targets at a numerical aperture less than 0.6. The numericalaperture of the system is preferably 0.05 to 0.4.

This summary and the following detailed description are merelyexemplary, illustrative, and explanatory, and are not intended to limit,but to provide further explanation of the invention as claimed.Additional aspects, features, objectives and advantages of the inventionwill be set forth in the descriptions that follow, and in part willbecome apparent from the written description, taken in conjunction withthe accompanying drawings, illustrating by way of example the principlesof the invention, or may be learned by practice of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features of the invention are set forth with particularity inthe appended claims. A better understanding of the features andadvantages will be facilitated by referring to the following detaileddescription that sets forth illustrative embodiments using principles ofthe invention, as well as to the accompanying drawings, in which likenumerals refer to like parts throughout the different views. Like parts,however, do not always have like reference numerals. Further, thedrawings are not drawn to scale, and emphasis has instead been placed onillustrating the principles of the invention. All illustrations areintended to convey concepts, where relative sizes, shapes, and otherdetailed attributes may be illustrated schematically rather thandepicted literally or precisely.

FIG. 1 illustrates a high-level flowchart in accordance with anembodiment of the present invention.

FIGS. 2A & B are illustrations of system embodiments.

FIG. 3 shows a flowchart of a method in accordance with an alternateembodiment.

FIG. 4 is an illustration of the line pattern applied across the lensfor depth ranging measurement (OCT, confocal reflection, confocalautofluorescence, ultrasound) of the axial profile of the anteriorchamber of the eye.

FIG. 5 is a top view diagram of a rotationally asymmetric capsulorhexisincision.

FIG. 6 is a top view diagram of a complementary rotationally asymmetricIOL.

FIG. 7 is a top view of the IOL of FIG. 6 positioned in the lens capsuleof FIG. 5.

FIGS. 8 and 9 are side views of the rotationally asymmetric IOL of FIG.6.

FIG. 10 illustrates fragmentation patterns of an ocular lens produced byone embodiment of the present invention.

FIG. 11 illustrates a line pattern 501 applied across the cornea 504 andlens for depth ranging measurement (OCT, confocal reflection, confocalautofluorescence, ultrasound) of the axial profile of the anteriorchamber of the eye. It goes over the iris 502 and the lens 402 (notshown)

FIG. 12 illustrates a measured scan pattern across the cornea and lenswhich can be used for depth ranging by OCT

FIG. 13 illustrates a measured scan pattern across the lens which can beused for depth ranging by confocal autofluorescence using a pulsed 320NM TO 430 NM laser.

FIG. 14 is another illustration of a system in accordance with anembodiment of this invention.

FIG. 15 shows a histological cross section of a corneal cut produced byone embodiment of the present invention in which no cavitation bubbleswere formed but the tissue was modified.

FIG. 16 shows a histological cross section of a opened corneal cut whichwas produced by one embodiment of the present invention in which nocavitation bubbles were formed as shown in FIG. 15. The cut opened upeffortless along the modified tissue structure.

FIG. 17 shows a histological cross section of a corneal cut produced byone embodiment of the present invention in which cavitation bubbles wereformed.

FIG. 18 shows an illustration of the refractive index changes 822locally induced to the corneal tissue 504 by said invention. As seen inFIG. 15 in this case no cavitation bubbles will be created. This effectwill induce a change of the refractive index profile of the cornealtissue.

FIG. 19 shows a high resolution SEM image of the excised human lenscapsule processed with the current invention. Compared to FIG. 20 thissample has a much smoother edge quality and does not show any effect ofcavitation bubbles.

FIG. 20 shows a high resolution SEM image of an excised human lenscapsule processed with a femtosecond laser. The effect of each singlelaser shot with spacing of 5 micrometer is visible as the mechanicaleffect of cavitation causes the rupture of the capsular tissue.

FIG. 21 is a graph of average power (W) of the laser as a function of NAwith 355 nm laser light at repetition rates of 70 kHz and 100 kHz,respectively. The time required to modify tissue, i.e., to complete acut, is also a function of the system NA.

FIG. 22 is a graph of the time required to modify tissue, i.e., “cuttime” per mm², as a function of NA with 355 nm light at repetition ratesof 70 kHz and 100 kHz, respectively.

FIG. 23 is a graph of a relative exposure ratio as a function of NA as afunction of NA with 355 nm light at repetition rates of 70 kHz and 100kHz, respectively.

FIG. 24 is a combination that combines the considerations of cut timeand iris exposure.

DETAILED DESCRIPTION OF ILLUSTRATED EMBODIMENTS

The present invention relates to method and systems for making anincision in eye tissue to alter its mechanical or optical properties.The following description is presented to enable one of ordinary skillin the art to make and use the invention and is provided in the contextof a patent application and its requirements. Various modifications tothe embodiments and the generic principles and features described hereinwill be readily apparent to those skilled in the art. Thus, the presentinvention is not intended to be limited to the embodiment shown but isto be accorded the widest scope consistent with the principles andfeatures described herein.

As shown in the drawings for purposes of illustration, a method andsystem for making an incision in eye tissue or alter its mechanical oroptical properties are disclosed. In varying embodiments, the method andsystem disclosed herein provide many advantages over the currentstandard of care. Specifically, rapid and precise openings in the lenscapsule are enabled using a 320 nm to 430 nm laser to facilitate theplacement and stability of intraocular lenses.

Other procedures enabled by the techniques described herein include thetreatment of astigmatism. Intraocular lens (IOLs) are typically used forcorrecting astigmatism but require precise placement, orientation andstability. Complete and long lasting correction using IOLs is difficult.It often involves further surgical intervention to make the cornealshape more spherical, or at least less radially asymmetrical. This canbe accomplished by making Corneal or Limbal Relaxing Incisions. Otherprocedures include the creation of corneal flaps for LASIK procedure andthe creation of matching corneal transplant shapes of the donor andrecipient cornea. The present invention may be employed to perform thesedelicate incisions.

FIG. 1 is a flowchart of a method in accordance with an embodiment. Afirst step 101 involves generating a beam of light from a 320 nm to 430nm laser system having at least a first pulse of light. A next step 102involves passing the beam of light through an optical element so thatthe beam of light is focused at a predetermined depth in the eye tissue.By implementing this method, rapid and precise openings in the lenscapsule are enabled thereby facilitating the placement and stability ofintraocular lenses.

The present invention can be implemented by a system 200 that projectsor scans an optical beam into a patient's eye 20, such as the systemshown in FIG. 2A. The system 200 includes control electronics 210, alight source 220, an attenuator 230, a beam expander 240, focusing lens'250, 260 and reflection means 270. Control electronics 210 may be acomputer, microcontroller, etc. Scanning may be achieved by using one ormore moveable optical elements (e.g. lenses 250, 260, reflection means270) which also may be controlled by control electronics 210, via inputand output devices (not shown). Another means of scanning might beenabled by an electro optical deflector device (single axis or dualaxis) in the optical path.

During operation, the light source 220 generates an optical beam 225whereby reflection means 270 may be tilted to deviate the optical beam225 and direct beam 225 towards the patient's eye 20. Focusing lens'250, 260 can be used to focus the optical beam 225 into the patient'seye 20. The positioning and character of optical beam 225 and/or thescan pattern it forms on the eye 20 may be further controlled by use ofan input device such as a joystick, or any other appropriate user inputdevice.

The present invention alternatively can be implemented by a system 700that additionally does a range finding of patient's eye 20, such as thesystem shown in FIG. 14. The system 700 includes control electronics210, a light source 220, an attenuator 230, a beam expander 701, anoptical variable beam attenuator 230, an separate focus lens combination704 and a beam reflection and scanning means 270. The light beam 225 oflight source 220 is focused through focusing lens 260 to its targetlocation 20. This will be controlled by electronics 210 which isconnected to deflection unit 270. Additionally the auto fluorescencelight 725 of the target structure 20 is de-scanned by the similaroptical path shared with laser light 225 by preferred means of adichroic beam splitter 703 and focused by a lens 720. An aperturepinhole 721 is placed in the focal spot of formed beam 725 as aconjugate of the laser beam (225) focus in target structure 20. Theintensity of the transmitted auto fluorescence light through beamaperture 721 is detected and converted to an electrical signal which canbe read by the control unit 210. Also an image of the treated area isimaged by lens 711 on an image capture device 710 which can be a CCD ora CMOS camera. Also this signal is transmitted to control unit 210.

In another variation of system 700 the detection combination unit 703,720, 721, 722 is used to confocally detect the back reflected light ofbeam 225 from sample 20.

The underlying mechanism of varying embodiment employs a 320 nm to 430nm laser source. The ultraviolet optical spectrum is technicallysubdivided into three major spectral regions which are: UVA (400 nm-315nm), UVB (315 nm-280 nm), UVC (280 nm-100 nm). Due to their high singlephoton energy, UVB and UVC light is commonly associated withcarcinogenic effects due to their ability to directly modify DNA. Whilewater is still transparent down to 200 nm the absorption of proteinsstrongly increases around 240 nm. This strong protein absorption in theUVC spectral region, which is also the leading absorption in cornealtissue, is clinically used nowadays in Laser-Assisted in situKeratomileusis (LASIK) procedures to precisely ablate the cornealtissue.

UVC lasers have been used to ablate biological tissue throughphotodissociation, the absorption of a high energy photon to break bondswithin an organic molecule. A list of such common bonds is given in thetable below along with their dissociation energies listed in terms ofwavelength. The shorter the wavelength, the stronger the bond.

Bond Energy (nm) C—H, sp3 292 C—H, sp 239 C═C 199

From this table it is obvious that highly energetic photons are requiredfor the photodissociation of biological materials, such as is discussedin U.S. Pat. No. 4,784,135 by Blum, et al. This effect is the basis ofnumerous photo-medical systems, especially in ophthalmology where 193 nmexcimer lasers are routinely used for corneal modification. Embodimentsof the present invention utilize an altogether different physicalphenomenon and different spectral region (UVA to green) to modify and orablate biological tissue that is neither present nor considered in theprior art.

In an embodiment, the light source 220 is a 320 nm to 430 nm lasersource such as an Nd:YAG laser source operating at the 3^(rd) harmonicwavelength, 355 nm. The transmission of the cornea at 355 nm is about85% and starts to strongly drop off at 320 nm (50% transmission) to 300nm with about 2% transmission whereas the lens absorption is ˜99%. Also,for older people, light scattering of the cornea is minimal while lightscattering of the lens has considerably increased (cataract).

The effect of light scattering is sensitive to wavelength. In case ofscatter centers smaller than the used wavelength, the scatteringcoefficient scales as λ⁻⁴. For larger scatterers with a size rangewithin the size of the wavelength, the Mie approximation is well suitedfor describing the scattering function. For particles with sizes between350 and 700 nm in size, the scattering coefficient scales as λ⁻¹. Theaged lens itself absorbs all wavelengths shorter than 420 nm and is astrong scatterer. This implies that shorter wavelengths can be used forthe laser cutting of the anterior part of the aged lens, especially thelens capsule, while serving to protect the retina by effectivelyattenuating the light ultimately disposed there.

Q-switched infrared lasers with energies of several milliJoule and inthe IR spectral range (1064 nm) are routinely employed to treatposterior cataract opacification. They do so by providing a reliableplasma formation directly behind the posterior lens capsule. Thesepulses create cavitation bubbles of several millimeters in size and peakpressures in the kilobar range. Mechanical effects of the cavitationbubbles with their sizes in the millimeter range are the limiting factorfor highly precise cutting in a liquid environment. In order to reducethe bubble size and commensurate mechanical side-effects that yieldincisions with poor edge quality and therefore poor mechanical strength,laser pulse energy must be significantly reduced. Such an interactionwould, however, be well suited for the application of lens conditioning.

Q-switched green lasers with energies of several milliJoule and severalnanoseconds pulse duration are routinely employed to treat open angleglaucoma of the eye. This therapy named Selective Laser Trabecuplasty(SLT) utilizes the specific targeting of the melanin chromophorenaturally present in the trabecular meshwork. The laser itself uses arelatively large 200 micrometer spot size to cover most of the targetissue area. The laser produces also a cavitation bubble around themelanin absorber but this effect is due to linear heating than plasmaformation as used in the posterior cataract treatment with Q-switched IRlaser pulses.

In an embodiment of the invention the use of UV wavelengths,significantly reduces the threshold for plasma formation and associatedformation of cavitation bubbles but also decreases the threshold energyrequired for linear absorption enhanced photodecomposition without theformation of cavitation bubbles for a few reasons. First, the focusedspot diameter scales linearly with wavelength which squares the peakradiant exposure within the focal plane. Second, the linear absorptionof the material itself allows an even lower threshold for plasmaformation or low density photodecomposition as initially more laserenergy is absorbed in the target structure. Third, the use of UV laserpulses in the nanosecond and sub-nanosecond regime enables linearabsorption enhanced photodecomposition and chromophore guidedionization.

Furthermore, this chromophore guided ionization strongly lowers thethreshold for ionization in case of plasma formation as well lowers thethreshold for low density photodecomposition for material modificationor alteration without cavitation even under very weak absorption. Due tothe high fluence densities even minimal linear absorption stronglylowers the threshold for an effect. It has been shown (Colombelli etal., Rev. Sci. Instrum. 2004, Vol 75, pp. 472-478) that the thresholdfor plasma formation and the generation of cavitation bubbles can belowered by an order of magnitude if one only changes from high puritywater to water with a physiologic NADH concentration of 38 mMol. Thelinear absorption also allows for the specific treatment of topical lensstructures (e.g. the lens capsule) as the optical penetration depth ofthe laser beam is limited by the linear absorption of the lens. This isespecially true for aged lenses which absorption in the UV-blue spectralregion increases strongly compared to young lenses.

Additionally in another embodiment of this invention the linearabsorption effect on the target structures can be even enhanced byapplying exogenouse chromophors. One such useful chromophore is trypanblue which is commonly used in surgery to stain the lens capsule in caseof the absence of the fundus red reflex. Trypan blue also has anincreased linear absorption at wavelengths shorter than 370 nm. Thislinear absorption further reduces the energy required to createdisclosed effect on the lens capsular surface.

This method can also be used for the alteration of the overallrefractive power of the human eye by:

i. Create cuts (incisions) within the cornea to change its shape toalter its refractive powerii. Modify the refractive index of the corneal tissue to induce a changeof its effective refractive power.iii. Modify the refractive index of an implanted synthetic IOL bywriting Fresnel lenses or such other similar into the IOL material tochange its effective refractive poweriv. Any combination of i, ii, & iii.

The present inventive system enables surgical techniques that includeutilizing a pulsed 320 nm to 430 nm laser to perform highly precisephysical modifications of ocular targets, including tissues (such aslens, lens capsule, cornea, etc.) and synthetic intraocular lensimplants. This can be done in two different operating regimes; with orwithout cavitation bubble formation. The sub-cavitation regime can alsobe used to modify the refractive index of ocular targets. Although thewavelengths used in the present invention are shorter or in the rangethan those associated with retinal blue light toxicity, the absorptionof the 320 nm to 400 nm laser light within the aged lens furtherminimizes the risk of retinal damage, as this light will be absorbed bythe lens volume. Furthermore, the risk of damaging the cornealendothelium or other corneal structures is also minimized. The thresholdpulse energy will be E_(th)=Φ*d²/4, where Φ is the threshold radiantexposure and d is the focal spot diameter. Here, the focal spotdiameter, d, is d=λF/D_(b) where λ is the wavelength, F is the focallength of the last focusing element and D_(b) is the beam diameter ofthe last lens. For stable and reproducible operation, pulse energyshould exceed the threshold by at least a factor of 2, however, theenergy level can be adjusted to avoid damage to the corneal endothelium.

The incident light of the laser used for the modification of the eyetissue generally has a wavelength of between 320 nm and 430 nm,preferably between 320 and 400 nm, preferably between 320 to 370 nm, andmore preferably between 340 nm and 360 nm. In many embodiments, thelaser light has a wavelength of 355 nm.

The pulse energy of laser pulses is generally between 0.010 and 5000. Inmany embodiments, the pulse energy will be between 0.1 μJ and 100 μJ, ormore precisely, between 0.1 μJ and 40 μJ, or between 0.1 μJ and 10 μJ,or between 0.5 μJ and 8 μJ.

A pulse repetition rate of the laser pulses is generally between 500 Hzand 500 kHz. In many embodiments, the pulse repetition rate is between 1kHz to 200 kHz, or between 1 KHz to 100 KHz.

Spot sizes of the laser pulses are generally smaller than 10 μm. In manyembodiments, the spot size is preferably smaller than 5 μm, typically0.5 μm to 3 μm. In some embodiments, the spot size is in the range of 1μm to 2 μm.

A pulse duration of the laser pulses is generally between 1 ps and 100ns. In many embodiments, the pulse duration is between 100 ps to 10 ns,or between 100 ps and 1 ns. In a preferred embodiment, the pulseduration is between 300 ps and 700 ps, preferably 400 ps to 700 ps.

In some embodiments, the beam quality, also referred to as M² factor, isbetween 1 and 1.3. The M² factor is a common measure of the beam qualityof a laser beam. In brief, the M² factor is defined as the ratio of abeam's actual divergence to the divergence of an ideal, diffractionlimited, Gaussian TEM₀₀ beam having the same waist size and location asis described in ISO Standard 11146.

A peak power density (irradiance), obtained by dividing the peak powerof the laser pulse by the area of the focused spot, is generallyexpressed in units of GW/cm². In general, the peak power density(irradiance) of the laser pulses should be sufficiently high to modifythe ocular tissue to be treated. As would be understood by thoseordinarily skilled in the art, the peak power density (irradiance)depends upon a number of factors, including the pulse energy, pulseduration, and focused spot size. Note that the wavelength indirectlyaffects the irradiance since the minimum focused spot size for any givenconvergence angle is proportional to the wavelength. The practicaleffect of this is that smaller focused spots can be easier to obtainwith a shorter wavelength. In some embodiments, a peak power densitygenerally in the range of 20 GW/cm² to 2000 GW/cm² will be used to cutocular tissue with 355 nm light. Note that the “peak” power density(irradiance=power per unit area) in a Gaussian beam is typicallycalculated using the beam diameter specified at the “1/e of peakintensity” width. In this case the average pulse power is calculatedfrom the pulse energy divided by the pulse duration at the full widthhalf maximum point. Then, the average irradiance in time, at thegeometric peak of the intensity profile (center of the beam) is thepower divided by the “1/e” beam diameter. This is the value representedin the ranges 20 GW/cm² to 2000 GW/cm². The true peak instantaneousirradiance and the center of the beam is actually higher due to the“Gaussian” like temporal shape of the pulse power.

The scan range of the laser surgical system is preferably in the rangeof 6 to 10 mm.

In many embodiments for the modification of ocular tissue, spot spacingbetween adjacent laser pulses is typically in the range of about 0.20 μmto 10 μm, preferably 0.2 μm to 6 μm.

A numerical aperture should be selected that preferably provides for thefocal spot of the laser beam to be scanned over a scan range of 6 mm to10 mm in a direction lateral to a Z-axis that is aligned with the laserbeam. The NA of the system should be less than 0.6, preferably less than0.5 and more preferably in a range of 0.05 to 0.4, typically between 0.1and 0.3. In some specific embodiments, the NA is 0.15. For each selectedNA, there are suitable ranges of pulse energy and beam quality (measuredas an M² value) necessary to achieve a peak power density (irradiance)in the range required to cut the ocular tissue. Further considerationswhen choosing the NA include available laser power and pulse rate, andthe time needed to make a cut. Further, in selection of an appropriateNA, it is preferable to ensure that there is a safe incidental exposureof the iris, and other ocular tissues, that are not targeted for cuts.

FIG. 21 is a graph of average power (W) of the laser as a function of NAwith 355 nm laser light at repetition rates of 70 kHz and 100 kHz,respectively. Laser power required to modify tissue, as a function ofNA, increases as the NA decreases. As such, smaller NA values generallylead to a potentially undesirable need for a larger (higher averagepower) laser. As shown in FIG. 21, average power is preferably less thanabout 4 W.

The time required to modify tissue, i.e., to complete a cut, is also afunction of the system NA. FIG. 22 is a graph of the time required tomodify tissue, i.e., “cut time” per mm², as a function of NA with 355 nmlight at repetition rates of 70 kHz and 100 kHz, respectively. The timeneeded for a cut of unit area (1 mm²) increases with increasing NA dueto lower threshold energies, and the consequent need for increasednumber of pulses. As shown in FIG. 22, increased NA tends to lead tolonger cut times, favoring lower NA systems from this perspective.

Further, these so-called “cut times” affect the exposure of non-targettissue that is incidentally exposed while making laser cuts in oculartissue. For instance, the limit of safe exposure of the iris whiletreating the cornea may be expressed according to the following formula:

L (J/cm²)=C×T ^(0.75),

wherein L is a safe limit of safe exposure, C is a constant and T is thetotal exposure time for modifying tissue. FIG. 23 is a graph of therelative exposure ratio as a function of NA as a function of NA with 355nm light at repetition rates of 70 kHz and 100 kHz, respectively. InFIG. 23, the relative exposure ratio is defined as a ratio of the actualdelivered exposure divided by the safe limit of exposure, L. In therelative exposure ratios of FIG. 23, values of C are normalized to matchthe exposure at 0.15 NA in order to illustrate the effects of varying NAon the relative exposure. As shown in FIG. 22, the relative exposureratio increases with decreasing NA.

FIG. 24 is a graph combining FIGS. 22 and 23, i.e., FIG. 24 combines theconsiderations of cut time and iris exposure. From FIG. 24, it can beseen that there is an optimum at an intermediate NA in the range of 0.05to 0.40, and preferably 0.1 to 0.3.

Table 1 and Table 2, below, show typical representative laser beamparameters in accordance with many embodiments of the present invention.

TABLE 1 wavelength (nm) 355 355 355 355 355 355 energy (uJ) 1 4 2.25 90.36 1.44 pulse rate (kHz) 70 100 70 100 70000 100 Pulse length (s)6.00E−10 6.00E−10 6.00E−10 6.00E−10 6.00E−10 6.00E−10 NA (1/e{circumflexover ( )}2) 0.15 0.15 0.1 0.1 0.25 0.25 M{circumflex over ( )}2(1/e{circumflex over ( )}2) 1.3 1 1.3 1 1.3 1 spot spacing (μm) 1 2 1.53 0.6 1.2 theta (rad, 1/e{circumflex over ( )}2) 0.3 0.3 0.2 0.2 0.5 0.5BP (μm, 1/e{circumflex over ( )}2) 0.588 0.452 0.588 0.452 0.587 0.452SS (μm, 1/e{circumflex over ( )}2) 1.95 1.5 2.94 2.26 1.18 0.904 area(mm{circumflex over ( )}2, 1/e{circumflex over ( )}2) 3.01E−06 1.78E−066.77E−06 4.01E−06 1.08E−06 6.42E−07 area (cm{circumflex over ( )}2,1/e{circumflex over ( )}2) 3.01E−08 1.78E−08 6.78E−08 4.01E−08 1.08E−086.42E−09 peak energy density 66.4 449 66.4 449 66.34 449(J/cm{circumflex over ( )}2) peak power density  1.E+11  7.E+11  1.E+11 7.E+11  1.E+11  7.E+11 (W/cm{circumflex over ( )}2) peak power density111 748 111 748 111 748 (GW/cm{circumflex over ( )}2) ratio to NS 100%100% 100% 100% 100% 100% average power (W) 0.07 0.4 0.158 0.9 0.02520.144 spots per mm{circumflex over ( )}2 1,000,000 250,000 444,000111,000 2,778,000 694,000 time per pattern mm{circumflex over ( )}2 (s)14.3 2.500 6.35 1.11 39.7 6.94 average pattern energy 100 100 100 100100 100 density (J/cm{circumflex over ( )}2) relative possible irissafety 353 95.4 192 51.9 758 205 limit (8*6T{circumflex over ( )}.75(J/cm{circumflex over ( )}2)) ratio energy density 0.284 1.05 0.521 1.930.132 0.487 delivered/safety

TABLE 2 wavelength (nm) 355 355 355 355 energy (uJ) 9 36 0.141 0.562pulse rate (Hz) 70000 100000 70000 100000 Pulse length (s) 6.00E−106.00E−10 6.00E−10 6.00E−10 NA (1/e{circumflex over ( )}2) 0.05 0.05 0.40.4 M{circumflex over ( )}2 (1/e{circumflex over ( )}2) 1.3 1 1.3 1 spotspacing (μm) 3 6 0.375 0.75 theta (rad, 1/e{circumflex over ( )}2) 0.10.1 0.8 0.8 BP (μm, 1/e{circumflex over ( )}2) 0.588 0.452 0.0588 0.452SS (μm, 1/e{circumflex over ( )}2) 5.88 4.52 0.735 0.565 area(mm{circumflex over ( )}2, 1/e{circumflex over ( )}2) 2.71E−05 1.61E−054.24E−07 2.51E−07 area (cm{circumflex over ( )}2, 1/e{circumflex over( )}2) 2.71E−07 1.61E−07 4.24E−09 2.51E−09 peak energy density(J/cm{circumflex over ( )}2) 66.4 449 66.4 449 peak power density(W/cm{circumflex over ( )}2)  1.E+11  7.E+11  1.E+11  7.E+11 peak powerdensity (GW/cm{circumflex over ( )}2) 111 748 111 748 ratio to NS100.00% 100.00% 100.00% 100.00% average power (W) 0.63 3.6 0.009840.0563 spots per mm{circumflex over ( )}2 111,000 27,800 7,111,0001,778,000 time per pattern mm{circumflex over ( )}2 (s) 1.59 0.278 10217.8 average pattern energy 100.000 100.000 100.000 100.000 density(J/cm{circumflex over ( )}2) relative possible iris 67.9 18.4 154 416safety limit (8*6T{circumflex over ( )}.75 (J/cm{circumflex over ( )}2))ratio energy density delivered/safety 1.47 5.45 0.065 0.241

In Tables 1 and 2, theta is the divergence half-angle, BP is the beamparameter product, SS is the spot size, and the area is the area of thelaser spot. Here, the 1/e² width is equal to the distance between thetwo points on the marginal distribution that are 1/e²=0.135 times themaximum value.

An example of the results of such a system on an actual humancrystalline lens is shown in FIG. 10. A beam of 4 μJ, 400 ps pulsesdelivered at a pulse repetition rate of 0.5 kHz from a laser operatingat a wavelength of 355 nm was focused at NA=0.15, using an irradiance ofabout 120 gigaWatts per square centimeter. This produced the capsulotomypatterns in the human lens shown in FIG. 10. In this case no cavitationbubbles were formed to induce the cuts. This was confirmed visuallyunder the microscope but also by using a hydrophone for the detection ofthe acoustic sound wave emitted by cavitation bubbles. For lasercataract surgery, the only high precision cut on the lens itself is thecapsulotomy. For the softening or fragmentation of the lens nucleus, thepatterns don't need a high spatial confinement. So for this applicationeven if there is a longer pulse, a higher fluence and/or irradiancethreshold is acceptable.

FIG. 3 shows a flowchart of a method in accordance with an alternateembodiment. A first step 301 involves generating a beam of light from a320 nm to 430 nm laser system. A next step 302 involves translating thefocused beam of light within the eye tissue in a controlled fashionthereby forming an incision. In an embodiment, the incision is formed inthe anterior lens capsule of the eye tissue in the performance of acapsulorhexis. Alternately, the incision may be in the cornea for thepurposes of astigmatic correct or creating surgical access. For example,clear corneal cataract instrumentation and paracentesis incisions maybeused to provide surgical access.

The control electronics 210 and the lights source 220 can be set totarget the surfaces of the targeted structures in the eye 20 and ensurethat the beam 225 will be focused where appropriate and notunintentionally damage non-targeted tissue. Imaging modalities andtechniques described herein, such as for example, Optical CoherenceTomography (OCT), Purkinje imaging, Scheimpflug imaging,autofluorescence imaging, confocal autofluorescence, confocalreflectance imaging or ultrasound may be used to determine the locationand measure the thickness of the lens and lens capsule to providegreater precision to the laser focusing methods, including 2D and 3Dpatterning. Laser focusing may also be accomplished using one or moremethods including direct observation of an aiming beam, OCT, Purkinjeimaging, Scheimpflug imaging, structured light illumination, ultrasound,or other known ophthalmic or medical imaging modalities and/orcombinations thereof. It should be noted that the imaging depth needonly include the anterior most portion of the intraocular target, andnot necessarily the entire eye or even the anterior chamber.

Additionally confocal reflectometry can be used for the adjustment ofdelivered laser energy during treatment as it will be able to detect ifa cavitation bubble is formed after a laser pulse and adjust the energyof subsequent laser pulses or monitor the laser induced change of therefractive index of said tissue.

Accordingly, a three dimensional application of laser energy can beapplied across the capsule along the pattern produced by thelaser-induced effect in a number of ways. For example, the laser can beemployed to produce several circular or other pattern scansconsecutively at different depths with a step equal to the axial lengthof the effect zone. Thus, the depth of the focal point (waist) in thetissue is stepped up or down with each consecutive scan. The laserpulses are sequentially applied to the same lateral pattern at differentdepths of tissue using, for example, axial scanning of the focusingelements or adjusting the optical power of the focusing element while,optionally, simultaneously or sequentially scanning the lateral pattern.

The adverse result of laser beam scattering on bubbles, cracks and/ortissue fragments prior to reaching the focal point can be avoided byfirst producing the pattern/focusing on the maximal required depth intissue and then, in later passes, focusing on more shallow tissuespaces. Not only does this “bottom up” treatment technique reduceunwanted beam attenuation in tissue above the target tissue layer, butit also helps protect tissue underneath the target tissue layer. Byscattering the laser radiation transmitted beyond the focal point on gasbubbles, cracks and/or tissue fragments which were produced by theprevious scans, these defects help protect the underlying retina.Similarly, when segmenting a lens, the laser can be focused on the mostposterior portion of the lens and then moved more anteriorly as theprocedure continues.

The present invention can be implemented by a system that projects orscans an optical beam into a patient's eye 68, such as system 2 shown inFIG. 2B which includes a TREATMENT light source 4 (e.g. a short pulsed355 nm laser). Using this system, a beam may be scanned in a patient'seye in three dimensions: X, Y, Z. Safety limits with regard tounintended damage to non-targeted tissue bound the upper limit withregard to repetition rate and pulse energy; while threshold energy, timeto complete the procedure and stability bound the lower limit for pulseenergy and repetition rate.

The laser 4 is controlled by control electronics 300, via an input andoutput device 302, to create optical beam 6. Control electronics 300 maybe a computer, microcontroller, etc. In this example, the entire systemis controlled by the controller 300, and data moved through input/outputdevice IO 302. A graphical user interface GUI 304 may be used to setsystem operating parameters, process user input (UI) 306 on the GUI 304,and display gathered information such as images of ocular structures.

The generated TREATMENT light beam 6 proceeds towards the patient eye 68passing through half-wave plate, 8, and linear polarizer, 10. Thepolarization state of the beam can be adjusted so that the desiredamount of light passes through half-wave plate 8 and linear polarizer10, which together act as a variable attenuator for the TREATMENT beam6. Additionally, the orientation of linear polarizer 10 determines theincident polarization state incident upon beamcombiner 34, therebyoptimizing beamcombiner throughput.

The TREATMENT beam proceeds through a shutter 12, aperture 14, and apickoff device 16. The system controlled shutter 12 ensures on/offcontrol of the laser for procedural and safety reasons. The aperturesets an outer useful diameter for the laser beam and the pickoffmonitors the output of the useful beam. The pickoff device 16 includesof a partially reflecting mirror 20 and a detector 18. Pulse energy,average power, or a combination may be measured using detector 18. Theinformation can be used for feedback to the half-wave plate 8 forattenuation and to verify whether the shutter 12 is open or closed. Inaddition, the shutter 12 may have position sensors to provide aredundant state detection.

The beam passes through a beam conditioning stage 22, in which beamparameters such as beam diameter, divergence, circularity, andastigmatism can be modified. In this illustrative example, the beamconditioning stage 22 includes a 2 element beam expanding telescopecomprised of spherical optics 24 and 26 in order to achieve the intendedbeam size and collimation. Although not illustrated here, an anamorphicor other optical system can be used to achieve the desired beamparameters. The factors used to determine these beam parameters includethe output beam parameters of the laser, the overall magnification ofthe system, and the desired numerical aperture (NA) at the treatmentlocation. In addition, the optical system 22 can be used to imageaperture 14 to a desired location (e.g. the center location between the2-axis scanning device 50 described below). In this way, the amount oflight that makes it through the aperture 14 is assured to make itthrough the scanning system. Pickoff device 16 is then a reliablemeasure of the usable light.

After exiting conditioning stage 22, beam 6 reflects off of fold mirrors28, 30, & 32. These mirrors can be adjustable for alignment purposes.The beam 6 is then incident upon beam combiner 34. Beamcombiner 34reflects the TREATMENT beam 6 (and transmits both the OCT 114 and aim202 beams described below). For efficient beamcombiner operation, theangle of incidence is preferably kept below 45 degrees and thepolarization where possible of the beams is fixed. For the TREATMENTbeam 6, the orientation of linear polarizer 10 provides fixedpolarization.

Following the beam combiner 34, the beam 6 continues onto the z-adjustor Z scan device 40. In this illustrative example the z-adjust includesa Galilean telescope with two lens groups 42 and 44 (each lens groupincludes one or more lenses). Lens group 42 moves along the z-axis aboutthe collimation position of the telescope. In this way, the focusposition of the spot in the patient's eye 68 moves along the z-axis asindicated. In general there is a fixed linear relationship between themotion of lens 42 and the motion of the focus. In this case, thez-adjust telescope has an approximate 2× beam expansion ratio and a 1:1relationship of the movement of lens 42 to the movement of the focus.Alternatively, lens group 44 could be moved along the z-axis to actuatethe z-adjust, and scan. The z-adjust is the z-scan device for treatmentin the eye 68. It can be controlled automatically and dynamically by thesystem and selected to be independent or to interplay with the X-Y scandevice described next. Mirrors 36 and 38 can be used for aligning theoptical axis with the axis of z-adjust device 40.

After passing through the z-adjust device 40, the beam 6 is directed tothe x-y scan device by minors 46 & 48. Minors 46 & 48 can be adjustablefor alignment purposes. X-Y scanning is achieved by the scanning device50 preferably using two mirrors 52 & 54 under the control of controlelectronics 300, which rotate in orthogonal directions using motors,galvanometers, or any other well known optic moving device. Minors 52 &54 are located near the telecentric position of the objective lens 58and contact lens 66 combination described below. Tilting these mirrors52/54 causes them to deflect beam 6, causing lateral displacements inthe plane of TREATMENT focus located in the patient's eye 68. Objectivelens 58 may be a complex multi-element lens element, as shown, andrepresented by lenses 60, 62, and 64. The complexity of the lens 58 willbe dictated by the scan field size, the focused spot size, the availableworking distance on both the proximal and distal sides of objective 58,as well as the amount of aberration control. An objective lens 58 offocal length 60 mm, operating over a field of 7 mm, with an input beamsize of 20 mm diameter is an example. Alternatively, X-Y scanning byscanner 50 may be achieved by using one or more moveable opticalelements (e.g. lenses, gratings) which also may be controlled by controlelectronics 300, via input and output device 302.

The aiming and treatment scan patterns can be automatically generated bythe scanner 50 under the control of controller 300. Such patterns may becomprised of a single spot of light, multiple spots of light, acontinuous pattern of light, multiple continuous patterns of light,and/or any combination of these. In addition, the aiming pattern (usingaim beam 202 described below) need not be identical to the treatmentpattern (using light beam 6), but preferably at least defines itsboundaries in order to assure that the treatment light is delivered onlywithin the desired target area for patient safety. This may be done, forexample, by having the aiming pattern provide an outline of the intendedtreatment pattern. This way the spatial extent of the treatment patternmay be made known to the user, if not the exact locations of theindividual spots themselves, and the scanning thus optimized for speed,efficiency and accuracy. The aiming pattern may also be made to beperceived as blinking in order to further enhance its visibility to theuser.

An optional contact lens 66, which can be any suitable ophthalmic lens,can be used to help further focus the optical beam 6 into the patient'seye 68 while helping to stabilize eye position. The positioning andcharacter of optical beam 6 and/or the scan pattern the beam 6 forms onthe eye 68 may be further controlled by use of an input device such as ajoystick, or any other appropriate user input device (e.g. GUI 304) toposition the patient and/or the optical system.

The TREATMENT laser 4 and controller 300 can be set to target thesurfaces of the targeted structures in the eye 68 and ensure that thebeam 6 will be focused where appropriate and not unintentionally damagenon-targeted tissue. Imaging modalities and techniques described herein,such as for example, Optical Coherence Tomography (OCT), Purkinjeimaging, Scheimpflug imaging, structured light illumination, confocalback reflectance imaging, fluorescence imaging, or ultrasound may beused to determine the location and measure the thickness of the lens andlens capsule to provide greater precision to the laser focusing methods,including 2D and 3D patterning, or other known ophthalmic or medicalimaging modalities and/or combinations thereof. In the embodiment ofFIG. 2A, an OCT device 100 is described, although other modalities arewithin the scope of the present invention. An OCT scan of the eye willprovide information about the axial location of the anterior andposterior lens capsule, the boundaries of the cataract nucleus, as wellas the depth of the anterior chamber. This information is then be loadedinto the control electronics 300, and used to program and control thesubsequent laser-assisted surgical procedure. The information may alsobe used to determine a wide variety of parameters related to theprocedure such as, for example, the upper and lower axial limits of thefocal planes used for modifying the lens capsule, cornea, and syntheticintraocular lens implant, among others.

The OCT device 100 in FIG. 2A includes a broadband or a swept lightsource 102 that is split by a fiber coupler 104 into a reference arm 106and a sample arm 110. The reference arm 106 includes a module 108containing a reference reflection along with suitable dispersion andpath length compensation. The sample arm 110 of the OCT device 100 hasan output connector 112 that serves as an interface to the rest of theTREATMENT laser system. The return signals from both the reference andsample arms 106, 110 are then directed by coupler 104 to a detectiondevice 128, which employs one of the following; time domain, frequencydomain, or single point detection techniques. In FIG. 2A, a frequencydomain technique is used with an OCT wavelength of 920 nm and bandwidthof 100 nm.

Exiting connector 112, the OCT beam 114 is collimated using lens 116.The size of the collimated beam 114 is determined by the focal length oflens 116. The size of the beam 114 is dictated by the desired NA at thefocus in the eye and the magnification of the beam train leading to theeye 68. Generally, OCT beam 114 does not require as high an NA as theTREATMENT beam 6 in the focal plane and therefore the OCT beam 114 issmaller in diameter than the TREATMENT beam 6 at the beamcombiner 34location. Following collimating lens 116 is aperture 118 which furthermodifies the resultant NA of the OCT beam 114 at the eye. The diameterof aperture 118 is chosen to optimize OCT light incident on the targettissue and the strength of the return signal. Polarization controlelement 120, which may be active or dynamic, is used to compensate forpolarization state changes which may be induced by individualdifferences in corneal birefringence, for example. Minors 122 & 124 arethen used to direct the OCT beam 114 towards beamcombiners 126 & 34.Mirrors 122 & 124 may be adjustable for alignment purposes and inparticular for overlaying of OCT beam 114 to TREATMENT beam 6 subsequentto beamcombiner 34. Similarly, beamcombiner 126 is used to combine theOCT beam 114 with the aim beam 202 described below.

Once combined with the TREATMENT beam 6 subsequent to beamcombiner 34,OCT beam 114 follows the same path as TREATMENT beam 6 through the restof the system. In this way, OCT beam 114 is indicative of the locationof TREATMENT beam 6. OCT beam 114 passes through the z-scan 40 and x-yscan 50 devices then the objective lens 58, contact lens 66 and on intothe eye 68. Reflections and scatter off of structures within the eyeprovide return beams that retrace back through the optical system, intoconnector 112, through coupler 104, and to OCT detector 128. Thesereturn back reflections provide the OCT signals that are in turninterpreted by the system as to the location in X, Y Z of TREATMENT beam6 focal location.

OCT device 100 works on the principle of measuring differences inoptical path length between its reference and sample arms. Therefore,passing the OCT through z-adjust 40 does not extend the z-range of OCTsystem 100 because the optical path length does not change as a functionof movement of 42. OCT system 100 has an inherent z-range that isrelated to the detection scheme, and in the case of frequency domaindetection it is specifically related to the spectrometer and thelocation of the reference arm 106. In the case of OCT system 100 used inFIG. 2A, the z-range is approximately 1-2 mm in an aqueous environment.Extending this range to at least 4 mm involves the adjustment of thepath length of the reference arm within OCT system 100. Passing the OCTbeam 114 in the sample arm through the z-scan of z-adjust 40 allows foroptimization of the OCT signal strength. This is accomplished byfocusing the OCT beam 114 onto the targeted structure whileaccommodating the extended optical path length by commensuratelyincreasing the path within the reference arm 106 of OCT system 100.

Because of the fundamental differences in the OCT measurement withrespect to the TREATMENT focus device due to influences such asimmersion index, refraction, and aberration, both chromatic andmonochromatic, care must be taken in analyzing the OCT signal withrespect to the TREATMENT beam focal location. A calibration orregistration procedure as a function of X, Y Z should be conducted inorder to match the OCT signal information to the TREATMENT focuslocation and also to the relate to absolute dimensional quantities.

Observation of an aim beam may also be used to assist the user todirecting the TREATMENT laser focus. Additionally, an aim beam visibleto the unaided eye in lieu of the infrared OCT and TREATMENT beams canbe helpful with alignment provided the aim beam accurately representsthe infrared beam parameters. An aim subsystem 200 is employed in theconfiguration shown in FIG. 2A. The aim beam 202 is generated by an aimbeam light source 201, such as a helium-neon laser operating at awavelength of 633 nm. Alternatively a laser diode in the 630-650 nmrange could be used. The advantage of using the helium neon 633 nm beamis its long coherence length, which would enable the use of the aim pathas a laser unequal path interferometer (LUPI) to measure the opticalquality of the beam train, for example.

It should be also noted that TREATMENT beam may also be attenuated tothe nanoJoule level and used instead of the OCT system described above.Such a configuration provides for the most direct correlation betweenthe position of the focal locations for imaging and treatment—they arethe same beam.

In this embodiment, the same laser assembly is used both for treatment(i.e. modification) and imaging of the target tissue. For instance, thetarget tissue may be imaged by raster scanning the pulsed laser beamalong the target tissue to provide for a plurality of data points, eachdata point having a location and intensity associated with it forimaging of the target tissue. In some embodiments, the raster scan isselected to deliver a sparse pattern in order to limit the patient'sexposure, while still discerning a reasonable map of the intraoculartargets. In these embodiments, the spacing between at least two adjacentlaser spots during an imaging raster scan of a target tissue is greaterthan a spot spacing of the adjacent laser spots in a treatment scan ofthe same target tissue. In order to image the target tissue, thetreatment laser beam (i.e. the laser beam having the parameters suitablychosen as described above for the modification of tissue) is preferablyattenuated to the nanoJoule level for imaging of the structures to betreated. When used for imaging, the attenuated laser beam may bereferred to as an imaging beam. In many embodiments, the treatment beamand the imaging beam may be the same except that the pulse energy of thelaser source is lower than the treatment beam when the laser beam isused for imaging. In many embodiments, the pulse energy of the laserbeam when used for imaging is preferably from about 0.1 nJ to 10 nJ,preferably less than 2 nJ and more preferably less than 1.8 nJ. The useof the same laser beam for both treatment and imaging provides for themost direct correlation between the position of the focal locations forimaging and treatment—they are the same beam. This attenuated imagingbeam can be used directly in a back reflectance measuring configuration,but, alternatively, may be used indirectly in a fluorescence detectionscheme. Since increases in both backscatter and fluorescence withintissue structures will be evident, both approaches have merit.

In a preferred embodiment, imaging of a first target area to be modifiedis performed sequentially with the modification of the tissue in thefirst target area before moving on to a second, different, target area,i.e. imaging is performed sequentially with treatment in a predeterminedtarget area. Thus, for instance imaging of the lens capsule ispreferably followed by treatment of the lens capsule before imaging iscarried out on other either structures, such as the cornea or iris. Inanother embodiment, imaging of a first target area where a firstincision to be place is performed sequentially with the scanning thetreatment beam to perform the incision in the first target area beforemoving on to a second target area for performing a second incision, i.e.imaging of the area to be incised is performed sequentially withscanning the treatment beam to perform in the predetermined target area.

In another embodiment, a cataract procedure comprises a capsulotomyincision, and at least one of a cataract incision and a limbal relaxingincision. In one embodiment, imaging of the target tissue where thecapsulotomy is to be performed is followed by scanning of the treatmentto perform the capsulotomy, and then the treatment beam is scanned toperform the capsulotomy. Subsequently, imaging of the target tissuewhere the at least one of the cataract incisions (CI) and the limbalrelaxing incision (LRI) is carried out and then the treatment beam isscanned to perform the at least one of the LRI and the CI. When an LRIis selected, this minimizes the chance for the patient to move betweenimaging and treatment for the LRIs which are the most critical/sensitiveto eye movements between image and treatment. Furthermore, since therequisite precision and inclusion size are much more relaxed for lensconditioning as compared to the incision of cornea and lens capsule, thepresent invention contemplates the addition of a short pulsed IR lasersource to the above described system for lens treatments, as wasmentioned above in the discussion of the use of milliJoule pulse fromQ-switched Nd:YAG lasers for the treatment of posterior opacification.Such pulse energies will cause larger inclusions, which unsuitable forcapsular and corneal incisions could provide for robust separation of acataractous lens. The NIR wavelength is not strongly absorbed orscattered by the lens, as opposed to shorter wavelengths. This secondtreatment source may have its beam combined with that of the firsttreatment beam by means of another beam splitter. The large differencein wavelength makes this a fairly straightforward design. However, thatsame spectral difference will require a different registration to theimaging and/or ranging modality, as was discussed above with respect toFIG. 2B.

FIG. 4 is an illustration of the line pattern applied across the lensfor OCT measurement of the axial profile of the anterior chamber of theeye 20. OCT imaging of the anterior chamber of the eye 20 can beperformed along a simple linear scan across the lens using the samelaser and/or the same scanner used to produce the patterns for cutting.This scan will provide information about the axial location of theanterior and posterior lens capsule, the boundaries of the cataractnucleus, as well as the depth of the anterior chamber. This informationmay then be loaded into the laser scanning system, and used to programand control the subsequent laser assisted surgical procedure. Theinformation may be used to determine a wide variety of parametersrelated to the procedure such as, for example, the upper and lower axiallimits of the focal planes for cutting the lens capsule and segmentationof the lens cortex and nucleus, the thickness of the lens capsule amongothers.

FIGS. 5 through 9 illustrate different aspects of an embodiment of thepresent invention, which can be implemented using the system 200described above. As shown in FIG. 5, a capsulorhexis incision 400 (whichmay be created using system 200) is tailored for astigmatism-correctingintraocular lenses (IOLs). Such astigmatism-correcting IOLs need to beplaced not only at the correct location within the capsule 402 of theeye 20, but also oriented at the correct rotational/clocking angle.Thus, they have inherent rotational asymmetries, unlike spherical IOLs.The incision 400 shown in this example is elliptical; however, othershapes are also useful. Incision 400 may be made continuously, orpiecewise to largely maintain the structural integrity of thelens-capsule apparatus of the patient's eye 20.

Such incomplete incisions 400 may be thought of as perforated incisions,and may be made to be removed gently in order to minimize theirpotential to inadvertently extend the capsulorhexis. Either way,incision 400 is an enclosed incision, which for the purposes of thisdisclosure means that it starts and ends at the same location andencircles a certain amount of tissue therein. The simplest example of anenclosed incision is a circular incision, where a round piece of tissueis encircled by the incision. It follows therefore that an enclosedtreatment pattern (i.e. generated by system 200 for forming an enclosedincision) is one that also starts and ends at the same location anddefines a space encircled thereby.

One key feature of the enclosed incision 400 is that it includes aregistration feature to orient the IOL that will be placed inside it.For the illustrated elliptical incision 400, it elliptical shape is it'sregistration feature, which allows for the accurate placement of an IOLby virtue of its inherent rotational asymmetry, unlike the desiredcircular outcome of a manual CCC. The elliptical major axis 404 andminor axis 406 of incision 400 are shown. Major axis 404 and minor axis406 are not equal. Incision 400 may be made at any rotational anglerelative to the eye 20 of a patient, although it is shown in thisexample to be in the plane of the iris with its major axis 404 lyingalong the horizontal. Incision 400 is intended to mate with one or morecomplementary registration features on an IOL. The system 200 may beused to precisely define the surface of the capsule 402 to be incised.This may serve to isolate the laser pulses nominally to the vicinity ofthe targeted capsule 402 itself, thus minimizing the energy required andthe treatment time and commensurately increasing patient safety andoverall efficiency.

As shown in FIG. 6, an IOL 408 includes an optic portion 410 used tofocus light and a haptic 416 used to position the IOL 408. Optic 410 isa rotationally asymmetric lens (about its optical axis) that include anelliptically shaped peripheral sidewall or edge 412, the complementaryregistration feature that mates with elliptically shaped incision 400.In this example, the elliptically shaped edge 412 includes a major axis418 and minor axis 420. Major axis 418 and minor axis 420 are not equal.IOL 408 further contains surface 414 that serves to hold haptics element416 and provide a resting place for capsule 402 to secure optic 410 ofintraocular lens 408 in the proper orientation and position within thecapsule 402 of a patient's eye 20. Surface 414 is shown as elliptical,but need not be.

Haptics 416 provide stability and may serve to seat edge 412 ofintraocular lens 408 in incision 400 by applying retaining force towardsthe anterior portion of capsule 402. Haptics 416 may be deployed in anyorientation. The orientation of the cylindrical correction of optic 410of intraocular lens 408 may be made to coincide with either its majoraxis 418 or its minor axis 420. In this way, intraocular lenses IOL 408and optic 410 may be manufactured in a standardized manner and therotational orientation of incision 400 and the spherical and cylindricaloptical powers of optic 410 may be made to vary to suit the individualoptical prescription of the eye 20 of a patient.

FIG. 7 shows the proper immediate disposition of intraocular lens 408once installed into capsule 402 with mating registration features edge412 and incision 400 engaged, and resting upon surface 414. Major axis404 and major axis 418 are not of equal length. Minor axis 406 and minoraxis 420 are not the same length, either. This is done to accommodatethe fact the capsule 402 may contract somewhat subsequent tocapsulorhexis incision. The difference between the lengths of these axesis intended to allow the capsule 402 to contract and still better seatintraocular lens 408 into capsule 402 via incision 400. Thesedifferences should be limited to allow for reasonable contraction, butnot so much as to allow for significant rotation of intraocular lens408. Typical values for these length differences may range from 100 μmto 500 μm, for example.

FIG. 8 shows a side view on the same intraocular lens 408 depicted inFIGS. 6 and 7. In this schematic representation, edge 412 is shown onthe same side of optic 410 as surface 424 of intraocular lens 408. Thesurface 422 on intraocular lens 408 serves to maintain the integrity offit between edge 412 and incision 400. Edge 412 is seen as theprojection of surface 422 in the alternate view depicted in FIGS. 6 and7. Optical axis 411 of optic 410 is shown. Haptics 416 lie along theline of sight in this view.

FIG. 9 is a side view of the lens configuration of FIG. 8, but rotated90 degrees to show that displaying surface 426 is not curved in bothdirections (i.e. shaped as a cylindrical lens). This cylindrical ortoric optical system of optic 410 provides cylindrical correction forthe astigmatism of a patient. Haptics 416 lie perpendicular to the lineof sight in this view.

As shown in FIG. 15 the system can also be used to alter the structureof for example corneal tissue without generating a cavitation bubble asshown in FIG. 16. These alterations of the corneal tissue can be used toshape the refractive index profile of the cornea 504 itself asillustrated in FIG. 18. A multitude of small localized modifications 822can be induced within the cornea which will change the refractiveprofile by altering the refractive index itself but also the mechanicalstrength of corneal tissue. So not only a change of index but also achange of corneal topography can be used. This is achieved by tightlycontrolling the lateral spacing of the laser effects utilizing beamdeflection units 270 and focus shifting unit 704 through focusing unit260.

As shown in the drawings for purposes of illustration, a method andsystem for making physical modifications (structural alterations) orincisions in eye tissue has been disclosed. In varying embodiments, themethod and system disclosed herein provide many advantages over thecurrent standard of care. Specifically, rapid and precise openings inthe lens capsule are enabled using a 320 nm to 430 nm laser tofacilitate the placement and stability of intraocular lenses. But alsothe alteration of the refractive power of the corneal tissue by locallyaltering the refractive index and reshaping the corneal topography.

Without further analysis, the foregoing so fully reveals the gist of thepresent inventive concepts that others can, by applying currentknowledge, readily adapt it for various applications without omittingfeatures that, from the standpoint of prior art, fairly constituteessential characteristics of the generic or specific aspects of thisinvention. Therefore, such applications should and are intended to becomprehended within the meaning and range of equivalents of thefollowing claims. Although this invention has been described in terms ofcertain embodiments, other embodiments that are apparent to those ofordinary skill in the art are also within the scope of this invention.

All patents and patent applications cited herein are hereby incorporatedby reference in their entirety.

The use of the terms “a” and “an” and “the” and similar referents in thecontext of describing the invention (especially in the context of thefollowing claims) are to be construed to cover both the singular and theplural, unless otherwise indicated herein or clearly contradicted bycontext. The terms “comprising,” “having,” “including,” and “containing”are to be construed as open-ended terms (i.e., meaning “including, butnot limited to,”) unless otherwise noted. The term “connected” is to beconstrued as partly or wholly contained within, attached to, or joinedtogether, even if there is something intervening. Recitation of rangesof values herein are merely intended to serve as a shorthand method ofreferring individually to each separate value falling within the range,unless otherwise indicated herein, and each separate value isincorporated into the specification as if it were individually recitedherein. All methods described herein can be performed in any suitableorder unless otherwise indicated herein or otherwise clearlycontradicted by context. The use of any and all examples, or exemplarylanguage (e.g., “such as”) provided herein, is intended merely to betterilluminate embodiments of the invention and does not pose a limitationon the scope of the invention unless otherwise claimed. No language inthe specification should be construed as indicating any non-claimedelement as essential to the practice of the invention.

While certain illustrated embodiments of this disclosure have been shownand described in an exemplary form with a certain degree ofparticularity, those skilled in the art will understand that theembodiments are provided by way of example only, and that variousvariations can be made without departing from the spirit or scope of theinvention. Thus, it is intended that this disclosure cover allmodifications, alternative constructions, changes, substitutions,variations, as well as the combinations and arrangements of parts,structures, and steps that come within the spirit and scope of theinvention as generally expressed by the following claims and theirequivalents.

1.-20. (canceled)
 21. A system for ophthalmic surgery of an eye of apatient, comprising: a laser source, configured to alternatively deliveran ultraviolet treatment laser beam and an ultraviolet probe laser beam,each laser beam comprising a plurality of ultraviolet laser pulses,wherein a pulse energy of the ultraviolet probe laser beam is lower thana pulse energy of the ultraviolet treatment laser beam; an opticalsystem operatively coupled to the laser source and configured to directthe laser beams; an imaging system operatively coupled to the lasersource and optical system and configured to detect a back reflectedlight from the eye; and a controller coupled to the laser source, theoptical system and the imaging system, and programmed to operate thelaser source, the optical system and the imaging system to: focus theultraviolet probe laser beam to a focal spot and direct the focal spotof the ultraviolet probe laser beam in a first imaging scan pattern intoa first intraocular target of the eye and to confocally detect backreflected light of the probe laser beam from the first intraoculartarget, thereby obtaining first image data corresponding to the firstintraocular target; thereafter, automatically generate a first treatmentscan pattern based at least in part on the first image data; andthereafter, focus the ultraviolet treatment laser beam to a focal spotand direct the focal spot of the ultraviolet treatment laser beam in thefirst treatment scan pattern into the first intraocular target, whereinthe ultraviolet treatment laser in the first treatment scan patternalters the first intraocular target; thereafter, focus the ultravioletprobe laser beam to a focal spot and direct the focal spot of theultraviolet probe laser beam in a second imaging scan pattern into asecond intraocular target of the eye which is different from the firstintraocular target, and to confocally detect back reflected light of theprobe laser beam from the second intraocular target, thereby obtainingsecond image data corresponding to the second intraocular target;thereafter, automatically generate a second treatment scan pattern basedat least in part on the second image data; and thereafter, focus theultraviolet treatment laser beam to a focal spot and direct the focalspot of the ultraviolet treatment laser beam in the second treatmentscan pattern into the second intraocular target, wherein the ultraviolettreatment laser in the second treatment scan pattern alters the secondintraocular target.
 22. The system of claim 21, wherein each of thefirst intraocular target and the second intraocular target is selectedfrom a group consisting of a cornea, a limbus, a sclera, a lens capsule,a crystalline lens, and a synthetic intraocular lens implant.
 23. Thesystem of claim 21, wherein the ultraviolet treatment laser in each ofthe first treatment scan pattern and the second treatment scan patterncreates one or more cuts in the corresponding first intraocular targetor second intraocular target, the one or more cuts being selected fromthe group consisting of one or more corneal relaxing incisions, one ormore limbal relaxing incisions, one or more astigmatic keratotomies, oneor more corneal flaps, one or more corneal transplant shapes, and one ormore capsulotomies.
 24. The system of claim 21, wherein the ultraviolettreatment laser in the first treatment scan pattern or the secondtreatment scan pattern changes an index of refraction of thecorresponding first intraocular target or second intraocular target. 25.The system of claim 21, wherein each of the ultraviolet treatment laserbeam and the ultraviolet probe laser beam has a wavelength between 320nanometers and 370 nanometers, wherein the ultraviolet treatment laserbeam has a pulse duration between 1 picosecond and 100 nanoseconds, anda pulse energy between 0.01 microJoules and 500 microJoules.
 26. Thesystem of claim 25, wherein the wavelength is 355 nm.
 27. The system ofclaim 25, wherein the pulse duration is between 400 picoseconds and 700picoseconds.
 28. The system of claim 25, wherein the pulse energy isbetween 0.5 microJoules and 10 microJoules.
 29. The system of claim 25,wherein each of the ultraviolet treatment laser beam and the ultravioletprobe laser beam has a repetition rate of between 500 Hertz and 500kiloHertz.
 30. The system of claim 25, wherein a diameter of the focalspot of each of the ultraviolet treatment laser beam and the ultravioletprobe laser beam is between 0.5 microns and 10 microns within the atleast one intraocular target.
 31. The system of claim 25, wherein anirradiance of the ultraviolet treatment laser beam at the focal spot isless than or equal to 120 gigawatts per square centimeter.
 32. Thesystem of claim 21, wherein the optical system has a numerical apertureof less than 0.6 and a scan range of 6 mm to 10 mm in a directionlateral to a Z-axis aligned with the laser beam.
 33. The system of claim32, wherein the numerical aperture of the system is 0.05 to 0.4.
 34. Thesystem of claim 21, wherein the controller is further programmed tooperate the imaging system to monitor for occurrence of a cavitationevent associated with formation of plasma, and in response to detectionof a cavitation event, to reduce the pulse energy of the treatment laserbeam or the probe laser beam.